The invention relates generally to the field of chemical synthesizers. More particularly, the invention provides devices, systems and methods for synthesizing various diverse chemical products onto solid supports, such as beads, cleaving the synthesized compounds from the beads and preparing samples for analysis.
Diverse chemical products find a wide variety of uses, such as in drug discovery, genetic studies and the like. Exemplary diverse chemical products that are useful in scientific studies include peptides, oligonucleotides, and other related materials.
The creation and analysis of diverse chemical products typically proceeds by synthesizing diverse collections of molecules onto a plurality of solid supports, such as beads. For many applications, it is desirable to simultaneously synthesize a wide variety of compounds onto the beads in a high throughput mode. In this manner, numerous compounds may be simultaneously synthesized in a single process, commonly referred to as parallel synthesis. To do so, a variety of synthesizers and techniques have been proposed, such as, for example, those described in copending U.S. application Ser. Nos. 08/146,886, filed Nov. 2, 1993, (Attorney Docket No. 16528-000730), and Ser. No. 08/722,657, filed Sep. 27, 1996, (Attorney Docket No. 16528A-022300), the disclosures of which are herein incorporated by reference.
During the process of synthesis, the beads (which are typically held within a well) are exposed to various liquids. For example, a typical process proceeds by exposing the beads to various reagents. Following this step, the beads are washed several times with a washing solution. Unfortunately, the introduction and removal of such liquids to and from the wells can be extremely time consuming and labor intensive. After the compounds have been synthesized, the compounds are usually cleaved from the beads, organized into samples and analyzed. Such steps are also time consuming and labor intensive since cleavage typically requires a cleavage solution to be introduced into the wells. Following cleavage, the removed compounds must then be organized into sample wells for analysis.
If is often preferable to transfer the cleaved compounds into the wells standard sized microtiter plates because such plates may then be used with most commercially available handling and processing equipment. For example, most automated plate readers, some speed vacuum concentrators, autosamplers, robotics liquid handling equipment, and the like require the samples to be placed into standard sized microtiter plates. However, the time and labor required to manually place samples into such plates can be extensive and considerably slow the process. Hence, the time required for actual synthesis of the compounds onto the beads is minimal compared to the other steps in the overall process, e.g., the introduction and removal of various liquids and chemicals to and from the reaction wells, the transfer of the cleaved compounds into sample wells, and the like.
Another important aspect of the synthesis process is the temperature of the reagents during their exposure to the beads. For example, in some cases it will be desirable to synthesize the compounds at controlled temperatures which are well above or well below room temperature. It may also be desirable in some cases to vary the temperature of the reagents in a controlled manner during synthesis. However, controlling the temperature in this manner can be difficult and challenging.
Therefore, it would be desirable to provide systems, devices and methods which would reduce the amount of time and labor required to complete such steps when simultaneously synthesizing large numbers of diverse compounds onto beads. It would be particularly desirable if such systems, devices and methods allowed for synthesis to occur using standard filling equipment so that the time and labor required to introduce and remove various liquids would be reduced. For example, it would be beneficial if standard multi-channel pipette systems or automated fluid delivery systems could be employed to introduce the various liquids into the reaction wells. It would also be desirable if the cleaved compounds could rapidly and efficiently be placed into the wells of standard sized microtiter plates so that the samples could be rapidly evaluated with commercially available handling and processing equipment. It would further be desirable to provide ways to control the temperature of the reagents during synthesis to provide for a wider assortment of synthesized compounds.